There is now increasing evidence that specific nucleic acid structures modulate gene expression. Understanding the structure-function relationships in nucleic acids requires innovative biophysical tools, in order to decipher how the nucleic acid sequence and the nucleic acid environment (e.g., binding of co-factors) modulates nucleic acid structures. Here we survey recent progress in ion mobility spectrometry to study nucleic acid structures, from intramolecular folds to higher-order structures: hairipins, duplexes, triplexes and G-quadruplexes. Gas-phase structures are very sensitive to internal energy effects caused by collisional in the source, upon introduction in the mobility cell, and inside travelling wave ion mobility cells. Extensive molecular dynamics simulations complement the ion-mobility mass spectrometry experiments, and outline which interactions are altered in the gas phase and which ones are conserved. Electrostatic interactions are predominant in the gas phase. On the one hand, non-native electrostatic interactions, not initially present in solution, can form in the gas phase and change the structure, as shown by simulation and experiments on hairpins and triplexes. On the other hand, hydrogen bonding motifs are well preserved in the gas phase. Furthermore, cation trapping in multiply charged anions help to preserve the gas phase structure of G-quadruplexes. In the case of G-quadruplexes, ion mobility spectrometry can therefore be used to decipher the composition of the solution. This is illustrated by changes in ion mobility following alteration of solution-phase conditions (changes of solvent, addition of ligands, folding time), in the case of telomeric DNA G-quadruplexes.

Ion mobility spectrometry of nucleic acid higher-order structures

246th National Meeting (2013)

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